Fecal-oral transmission of SARS-CoV-2: A systematic review of evidence from epidemiological and experimental studies

BACKGROUND: SARS-CoV-2 ribonucleic acid (RNA) has been detected in feces, but RNA is not infectious. This systematic review aims to answer if fecal SARS-CoV-2 is experimentally infectious and if evidence of human fecal-oral SARS-CoV-2 transmission exists. METHODS: On September 19, 2022, we searched PubMed, Embase, Web of Science, medRxiv, and bioRxiv. Biomedical studies inoculating SARS-CoV-2 from feces, rectal, or anal swabs in cells, tissue, organoids, or animals were included. Epidemiological studies of groups differing in exposure to fecal SARS-CoV-2 were included. Risk of bias was assessed using standardized tools. Results were summarized by vote counting, tabulation, and a harvest plot. PROSPERO registration no. CRD42020221719. RESULTS: A total of 4,874 studies were screened; 26 studies were included; and 13 out of 23 biomedical studies (56.5%) succeeded in infection. Two (66.7%) epidemiological studies found limited evidence suggesting fecal-oral transmission. All studies had concerns about the risk of bias. CONCLUSIONS: It is possible to experimentally infect cell cultures, organoids, and animals with fecal SARS-CoV-2. No strong epidemiologic evidence was found to support human fecal-oral transmission. We advise future research to study fecal infectivity at different time points during infection, apply appropriate controls, use in vivo models, and study fecal exposure as a risk factor of transmission in human populations.